..These studies establish oxidative damage as an early event in the pathogenesis of Alzheimer disease that can serve as a therapeutic target to slow the progression or perhaps the onset of the disease...

William R MarkesberyDepartment of Pathology and Laboratory Medicine, Sanders Brown Center on Aging, and Alzheimer s Disease Center, University of Kentucky College of Medicine, University of Kentucky, Lexington, Kentucky 40536 0230, USAJ Alzheimers Dis 19:221-8. 2010

..In early AD, the phase following MCI, the significant change is an increase in neurofibrillary tangles in the neocortex that correlates with an increase in Braak score and the observed clinical progression...

Mutations in amyloid precursor protein and presenilin-1 genes increase the basal oxidative stress in murine neuronal cells and lead to increased sensitivity to oxidative stress mediated by amyloid beta-peptide (1-42), HO and kainic acid: implications for

..The results are consonant with the hypothesis that Abeta(1-42)-associated oxidative stress and increased vulnerability to oxidative stress may contribute significantly to neuronal apoptosis and death in familial early onset AD...

..These results are discussed with reference to the importance of Abeta42-associated oxidative stress in the pathogenesis of AD...

Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease

..We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD...

..The identification of common oxidized proteins in different brain regions of AD brain suggests a potential role for these oxidized proteins and thereby oxidative stress in the pathogenesis of Alzheimer's disease...

Seleno-L-methionine protects against beta-amyloid and iron/hydrogen peroxide-mediated neuron death

..However, these trials produced intriguing data suggesting that the beneficial effects of omega-3 fatty acid supplementation may depend on the stage of disease, other dietary mediators, and apolipoprotein E status...

..Our data show that there are many important contributory causes to cognitive decline in older persons. However, NFTs and NPs should not be dismissed as irrelevant in AD based on clinicopathologic correlation...

Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship

..Overall, our results suggest that decreased OGG1 activity occurs early in the progression of AD, possibly mediated by 4-hydroxynonenal inactivation and may contribute to elevated 8-OHdG in the brain in MCI and LAD...

Quantitative changes in the mitochondrial proteome from subjects with mild cognitive impairment, early stage, and late stage Alzheimer's disease

..Our data suggest that further work is needed to refine our ability to identify specific aging-related brain disease mechanisms, especially in DLB...

Comparison of recruitment efforts targeted at primary care physicians versus the community at large for participation in Alzheimer disease clinical trials

Sarah A CarrDepartment of Neurology, University of Kentucky College of Medicine, Lexington, KY 40536, USAAlzheimer Dis Assoc Disord 24:165-70. 2010

..Our results suggest that outreach efforts directed at the potential study subject/caregiver are not only cost-effective but are able to easily accomplish the desired result of direct recruitment into clinical research studies...

Brains with medial temporal lobe neurofibrillary tangles but no neuritic amyloid plaques are a diagnostic dilemma but may have pathogenetic aspects distinct from Alzheimer disease

..5). Overall, these data suggest that organic Se can reduce Abeta burden and minimize DNA and RNA oxidation and support a role for it as a potential therapeutic agent in neurologic disorders with increased oxidative stress...

..There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes...

..Elevations of proteins associated with energy production suggest that cells undergoing Abeta-mediated apoptosis increase synthesis of proteins essential for ATP production and efflux in an attempt to maintain metabolic function...

Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease

..The presence of Msi-1 in a significant percentage of neurons containing cytoplasmic inclusions in 2 different neurodegenerative diseases suggests that it may play a role in the pathogenesis of these lesions...

Biophysical and biochemical characterization of the intrinsic fluorescence from neurofibrillary tangles

..The induced fluorophore, thus, has unique properties, and its generation likely depends on the particular conformation of paired helical filaments, which may in turn depend on tau hyperphosphorylation...

..This framework is illustrated by PREADVISE, a recently initiated large add-on prevention trial investigating the use of anti-oxidants for preventing AD among men enrolled in a even larger prostate cancer prevention study, SELECT...

Wilms' tumor suppressor (WT1) is a mediator of neuronal degeneration associated with the pathogenesis of Alzheimer's disease

Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer's disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development

..Larger head circumference (HC) may therefore be associated with later detection and diagnosis of AD. We investigated HC in nondemented individuals and AD patients using cross-sectional and prospective analyses...

..This review discusses current evidence supporting the role of oxidative stress/damage mediated apoptosis in in vitro models of neurodegeneration...

Small head circumference is associated with less education in persons at risk for Alzheimer disease in later life

James A MortimerDepartment of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL 33612 3805, USAAlzheimer Dis Assoc Disord 22:249-54. 2008

..These findings suggest that small HC limits educational attainment only among individuals who have greater risk of AD owing to their APOE genotype or who are destined to develop this illness later in life...

Head circumference, education and risk of dementia: findings from the Nun Study

James A MortimerInstitute on Aging, University of South Florida, Tampa, FL 33612 3899, USAJ Clin Exp Neuropsychol 25:671-9. 2003

..The findings suggest that higher education and larger head size, alone or in combination, may reduce the risk of expressing dementia in late life...

Healthy ageing in the Nun Study: definition and neuropathologic correlates

..Conceivably, altered DNA-histone interactions, subsequent to oxidative modification of histones by the lipid peroxidation product HNE, may contribute to the vulnerability of DNA to oxidation in AD brain...

..These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD, and that CSF F2-IsoPs may aid in the assessment of antioxidant experimental therapeutics and laboratory diagnosis of AD...

..0 (P = 0.02). Olfactory dysfunction is associated with ILB. If incidental Lewy bodies represent presymptomatic stage of PD, olfactory testing may be a useful screening tool to identify those at high risk for developing PD...

Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's disease

..Immunohistochemistry analysis of hippocampus confirmed this result. These findings suggest that nitrosative damage occurs early in the course of MCI, and that protein nitration may be important for conversion of MCI to AD...